Southampton's Jay Rodriguez will miss the next six months after rupturing his anterior cruciate ligament and could be joined on the sidelines for Cardiff's visit this weekend by several other first-team players.
The England international suffered the injury during last weekend's 4-1 defeat at Manchester City - a match which Gaston Ramirez (ankle) and Artur Boruc (back) missed through injury.
The pair will be assessed before Saturday's match, which back-up goalkeeper Kelvin Davis is likely to sit out due to a hip problem. Maya Yoshida (knee) is a long-term absentee.
Cardiff suffered a 3-0 home defeat to Crystal Palace last time out but boss Mauricio Pochettino, whose side sit comfortably in eighth, will not be taking them for granted.
"The motivation is always there because we have to defend to the death our colours, our shirt," he said.
"That's what we aim to do in every single game.
"We want to get the maximum number of points out of any season and it's a motivation for these players to be the first players at this football club to get this maximum number of points in the Premier League.
"We also need to look at the growth of this team and of every single player. Those two factors are a massive motivation for us."
Meanwhile, Cardiff manager Ole Gunnar Solskjaer has presented a united front at the Welsh club after reports that their starting line-up might have been leaked to Palace ahead of last Saturday's clash.
Solskjaer dismissed any suggestion of involvement by any member of the Cardiff squad.
The club, meanwhile, confirmed on Friday that chairman Mehmet Dalman has been in contact with the Premier League over an incident arising from the Palace game.
It is understood Cardiff have complained about the circumstances surrounding the alleged leaking of their team.
Palace sporting drector Iain Moody worked for Cardiff until earlier this season. He took up a post at Palace last November.
It has been reported that Cardiff believe Moody might have used his contacts at the Welsh club, or close to Cardiff, to find out which players would start against Palace.
Moody, though, has refuted the allegations, telling The Sun: "That is incredibly, extraordinarily untrue. That is untrue, completely untrue."
Cardiff are currently six points adrift of Premier League safety, lying 19th ahead of Saturday's trip to Southampton with just five games left.
Asked about the allegations at his pre-Southampton press conference on Friday, Solskjaer said: "My week has been on how we can give ourselves the best chance against Southampton.
"I think I have seen every one of my players and I don't doubt anyone's pride, honesty, loyalty, integrity, professionalism. They have all been fantastic this week.
"I have built my life on loyalty and honesty, and those are the values I get from my mum and dad. But in football you need to stick together and learn together, and this week has proved that more than anything.
"I have just said I have no reason to doubt any of my player's professionalism, or honesty, integrity or loyalty.
"I have said what I have said, and the rest will come from Mehmet.
"I am not talking about Crystal Palace. We've got Southampton, and that's my job to get ready for that game. When you are in a football club, you stick together. That's the key."
Cardiff will be without winger Craig Noone, who is set to miss the rest of this season due to an abdominal injury.
Striker Kenwyne Jones could also miss out at St Mary's after taking a blow to the kidneys against Palace.